Researchers at the University of California, Davis have developed RNA-based therapeutics to treat Wnt5A-expressing cancers, including treatment-resistant prostate cancer.
The Wnt gene family plays a significant role in human development – from embryogenesis through to their role in human diseases. Abnormal Wnt signaling has been linked to a variety of human maladies – including Robinow syndrome and abnormalities in bone density and retinal conditions. The Wnt5a gene in particular has been implicated as having a role in diseases including rheumatoid arthritis, tuberculosis, atherosclerosis and several types of cancer. The gene also plays important roles in multiple cellular processes directly related to promoting cancer progression and increasing cell resistance to chemotherapies.
Several previous strategies have been explored for targeting Wnt signaling in cancer. But none of them could directly target noncanonical Wnt/Wnt5A signaling. Some small, interfering, RNA (siRNA) approaches have also been attempted. However, unfavorable side effects and poor pharmacokinetic properties have often proven to be major drawbacks to this approach as well. Thus, the development of improved, effective, strategies for targeting the Wnt5A gene in order to treat cancer and overcome therapy resistance is an urgent need.
Researchers at the University of California, Davis have developed several bioengineered, siRNA therapeutics that block Wnt5A expression, inhibit cancer cell growth and help to overcome resistance to various cancer treatments. These therapeutics have proven particularly effective at inhibiting the growth of advanced prostate cancer cells while mitigating the traditional side effects associated with other siRNA approaches. This nanotherapeutic method has been shown to be effective in overcoming treatment resistance in preclinical models.